MGMT (O6-Methylguanine-DNA Methyltransferase) Gene Methylation Assay

CPT: 81287; 88381
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Test Details

Synonyms

  • O6-Methylguanine-DNA Methyltransferase (MGMT)

Use

MGMT (O6-methylguanine-DNA methyltransferase) is a DNA repair enzyme that is involved in the repair of damage caused by a variety DNA cross-linking compounds, including alkylating agents. Increased methylation of the MGMT gene promoter region causes diminished or silenced expression of the gene, making cells more sensitive to DNA damage. The relationship has been shown for glioblastomas and alkylating agents such as temozolomide (Temodar®).

Limitations

Preparation of DNA from tissue samples is dependent upon the quality of the provided specimen. Inadequate DNA extraction may occur in a significant number of paraffin-embedded samples.

Methodology

Quantitative methylation-specific polymerase chain reaction (PCR)

Additional Information

Approximately 40% to 50% of glioblastoma multiforme (GBM) tumors exhibit MGMT gene methylation. Retrospective studies have shown that detection of MGMT promoter methylation in tumor samples is associated with an increased likelihood of a favorable response to temozolomide.

Specimen Requirements

Specimen

Formalin-fixed, paraffin-embedded (FFPE) tissue blocks or slides.

Volume

FFPE tissue block or four unstained slides at 5 μM and one matching H&E slide or five precut unstained slides from a paraffin block in 5-μM sections.

Minimum Volume

Two unstained slides at 5 μM and one matching H&E slide or three unstained slides at 5 μM (Note: Samples with >4 mm² and ≥50% tumor content are preferred.)

Collection

FFPE tissue block or four unstained slides at 5 μM and one matching H&E slide or five precut unstained slides from a paraffin block in 5-μM sections.

Storage Instructions

Maintain blocks/slides at room temperature.

Causes for Rejection

Tumor block containing insufficient tumor tissue; tumor fixed in a heavy metal fixative; broken or stained slides

Clinical Information

Special Instructions

This assay is not approved for New York State residents.

Please provide a copy of the pathology report. Sample submission without a copy of the pathology report may delay testing. Please direct any questions regarding this test to customer service at 800-345-4363.

References

Brandes AA, Franceschi E, Tosoni A, et al. MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. J Clin Oncol. 2008 May 1; 26(13):2192-2197.18445844
Hau P, Stupp R, Hegi ME. MGMT methylation status: The advent of stratified therapy in glioblastoma? Dis Markers. 2007; 23(1-2):97-104.17325429
Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10; 352(10):997-1003.15758010
Vlassenbroeck I, Califice S, Diserens AC, et al. Validation of real-time methylation-specific PCR to determine O6-methylguanine-DNA methyltransferase gene promoter methylation in glioma. J Mol Diagn. 2008 Jul; 10(4):332-337.18556773

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